5‐HYDROXYTRYPTOPHYL PEPTIDES: POTENT INHIBITORS OF A STORAGE COMPARTMENT OF SEROTONIN 1
5‐HYDROXYTRYPTOPHYL PEPTIDES: POTENT INHIBITORS OF A STORAGE COMPARTMENT OF SEROTONIN 1
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5-羟基色氨酸肽：血清素 1 储存室的有效抑制剂
DOI：
10.1111/j.1471-4159.1979.tb00389.x
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发表时间：
1979
影响因子：
4.7
通讯作者：
M. Wilchek
中科院分区：
文献类型：
--
作者：
H. Tamir;M. Wilchek
测试了5-羟基色氨酸的几种类似物抑制5-羟色胺与5-羟色胺结合蛋白（SBP）结合的能力，SBP是一种在多巴胺能神经元中发现的对5-羟色胺具有高亲和力的蛋白质。发现N-取代的二肽N-乙酰基-5-羟基色氨酸-5-羟基色氨酸酰胺是这种结合的抑制剂。抑制（1.0 μM时50%）具有特异性，因为它不影响其他已知的5-羟色胺结合位点。5-羟色胺与其膜受体的结合不受二肽（高达10 μM）的影响。突触体对5-羟色胺的摄取仅受到轻微影响（10 μM时为9%），芳香族-L-氨基酸羧基裂解酶（EC 4.1.1.28）和胺：氧氧化还原酶（脱氨基）（含黄素）（EC 1.4.3.4）未受到抑制（分别为10 μM和5 mM）。脑或肌间神经丛的honiogenates未水解该肽。14 C标记的二肽被突触体摄取。然而，肽的摄取不受抑制5-羟色胺摄取的药物或5-羟色胺本身的影响，尽管过量的5-羟色氨酸消除了摄取。脑室内注射N-乙酰基二肽引起双相效应，这取决于剂量。较低剂量（10 nmol）诱导5-羟色胺脑水平下降（40%）。较高剂量（300 nmol）导致血清素水平增加95%。
Several analogues of 5‐hydroxytryptophan were tested for their ability to inhibit the binding of serotonin to serotonin‐binding protein (SBP), a protein found within serotonergic neurons which has a high affinity for serotonin. An N‐substituted dipeptide, N‐acetyl‐5‐hydroxytryptophan‐5‐hydroxytryptophan amide, was found to be an inhibitor of this binding. The inhibition (50% at 1.0 μM) was specific, since it did not affect other known sites of serotonin binding. The binding of serotonin to its membrane receptor was not affected by the dipeptide (up to 10 μM). Uptake of serotonin by synaptosomes was only slightly affected (9% at 10 μM), and aromatic‐L‐amino‐acid carboxy‐lyase(EC 4.1.1.28) and amine: oxygen oxidoreductase (deaminating) (flavin‐containing) (EC 1.4.3.4) were not inhibited (10 μM and 5 mM respectively), The peptide was not hydrolyzed by honiogenates of brain or myenteric plexus. The 14C‐labelled dipeptide was shown to be taken up by synaptosomes. However, the uptake of the peptide was not affected either by drugs that inhibit serotonin uptake or by serotonin itself although the uptake was abolished by excess 5‐hydroxytryptophan. Intraventricular injection of N‐acetyl dipeptide caused a biphasic effect depending on dose. Lower doses (10nmol) induced a decrease in serotonin brain levels (40%). Higher doses (300 nmol) caused a 95% increase in serotonin levels.